Many human skin diseases display a hyperproliferative or proliferative epidermis, or cutaneous inflammation, or combinations of these two pathological characteristics. As an example, the keratinocytes of the psoriatic epidermis are both hyperproliferative and produce elevated levels of the Amphiregulin EGF-like growth factor, and the IL-8, ILalpha and TNF-alpha cytokines, which could both attract and activate inflammatory cells, and promote psoriatic epidermal keratinocyte hyperproliferation. Additionally, the aberrant activity of the immune system may direct the mitogenic activation of these cells by activating the endogenous epidermal growth factor (EGF) pathway in the psoriatic epidermal keratinocytes. Our proposed investigation will examine activity of charged polymeric compounds that may block the EGF pathway in human keratinocyte cultures and penetrate into reconstructed human epidermis the results of the proposed study will determine whether these charged compounds might represent new non-steroidal drugs for further testing as therapeutics for inflammatory-proliferative human skin disease such as psoriasis and dermatitis. PUBLIC HEALTH RELEVANCE: This proposal is designed to synthesize and test new drugs for the treatment of the commonly observed human inflammatory-proliferative skin diseases such as psoriasis and dermatitis. It is hoped that the results of this study will produce new, safe and effective topical therapies for individuals suffering from these common skin diseases.